Astragaloside IV Inhibits Adipose Lipolysis and Reduces Hepatic Glucose Production via Akt Dependent PDE3B Expression in HFD-Fed Mice

被引:32
作者
Du, Qun [1 ]
Zhang, Shuihong [2 ]
Li, Aiyun [3 ]
Mohammad, Imran S. [4 ]
Liu, Baolin [2 ]
Li, Yanwu [1 ]
机构
[1] Guangzhou Univ Chinese Med, Pi Wei Inst, Guangzhou, Guangdong, Peoples R China
[2] China Pharmaceut Univ, Dept Pharmacol Chinese Materia Med, Jiangsu Key Lab TCM Evaluat & Translat Res, Nanjing, Jiangsu, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Expt Ctr Sci & Technol, Shanghai, Peoples R China
[4] China Pharmaceut Univ, Dept Pharmaceut, Nanjing, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
astragaloside IV; Akt; PDE3B; lipolysis; gluconeogenesis; NUCLEOTIDE PHOSPHODIESTERASE 3B; ENDOPLASMIC-RETICULUM STRESS; HORMONE-SENSITIVE LIPASE; INSULIN-RESISTANCE; PHOSPHORYLATION; SUPPRESSION; ACTIVATION; TISSUE; ALPHA; FAT;
D O I
10.3389/fphys.2018.00015
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Objective: This study aims to investigate the effect of astragaloside IV on adipose lipolysis and hepatic gluconeogenesis. Methods: High-fat diet (HFD) feeding induced adipose dysfunction with enhanced endogenous glucose production in mice. The effects of Astragaloside IV on lipolysis and hepatic glucose production were investigated. Results: HFD feeding induced cAMP accumulation through reducing PDE3B expression and activity in adipose tissue. As a result, HFD feeding increased adipose lipolysis in mice. Astragaloside IV enhanced Akt phosphorylation and promoted Akt binding to PDE3B to preserve PDE3B content, resultantly reducing adipose cAMP accumulation. Knockdown of Akt1/2 diminished the effect of astragaloside IV on PDE3B induction, indicative of the role of Akt in astragaloside IV action. As a result from blocking of cAMP/PKA signaling, astragaloside IV suppressed hormone-sensitive lipase (HSL) activation and inhibited inflammation-associated adipose lipolysis. Moreover, astragaloside IV reduced ectopic fat deposition in the liver and inhibited FoxO1 activation via regulation of Akt, resultantly restraining excess hepatic glucose production. Conclusion: We showed that preserving PDE3B content by Akt is a key regulation to prevent lipolysis. Astragaloside IV inhibited lipolysis by reducing cAMP accumulation via regulation of Akt/PDE3B, contributing to limiting hepatic lipid deposition and restraining excessive hepatic glucose production.
引用
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页数:12
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